Atherosclerotic cardiovascular disease (ASCVD) is a group of conditions that are caused by atherosclerosis and that can affect different locations throughout the body. Examples of ASCVD include coronary artery disease (CAD), peripheral artery disease (PAD), and ischemic stroke. Major risk factors include advanced age, smoking, diabetes mellitus, hypertension, and dyslipidemia. The pathogenesis of atherosclerosis is precipitated by endothelial damage, which leads to inflammation and the formation of atheromas in vessel walls. The risk of ASCVD should be estimated using an ASCVD risk calculator like the pooled cohort equations (PCE) to guide timely primary prevention strategies, such as lifestyle modifications and prophylactic statin therapy. Management of ASCVD involves intensive lifestyle modifications and high-intensity statin therapy, with or without antiplatelet therapy, to minimize the risk of future cardiovascular events.
ASCVD is an umbrella term for clinical manifestations of atherosclerosis that include: 
- Arteriosclerosis: an umbrella term to describe arterial wall thickening (hardening) and elasticity loss with variable pathogenesis
- Monckeberg arteriosclerosis
Arteriolosclerosis: the thickening and loss of elasticity of the small arteries and arterioles
- Hyaline arteriolosclerosis
- Hyperplastic arteriolosclerosis
Pathogenesis of atherosclerosis 
- Chronic stress on the endothelium (e.g., due to arterial hypertension and turbulence)
Endothelial cell dysfunction, which leads to:
- Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
- Adhesion of platelets to the damaged vessel wall → platelet release of inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)
- PDGF stimulates the migration and proliferation of smooth muscle cells (SMCs) in the tunica intima and mediates the differentiation of fibroblasts into myofibroblasts
- Inflammation of the vessel wall
- Macrophages and SMCs ingest cholesterol from oxidized LDL; and transform into foam cells (macrophages filled with lipid droplets).
- Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
- Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) deposition → development of a fibrous plaque (atheroma)
- Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
- Calcification of the intima (the amount and pattern of calcification affect the risk of complications)
- Plaque rupture → exposure of thrombogenic material ; (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material
Common sites (in order of frequency)
Atherosclerotic diseases 
- Weakening of vessel wall: arterial aneurysm or dissection (e.g., aortic aneurysm, aortic dissection)
- Demand-supply mismatch: coronary heart disease (e.g., coronary artery disease, stable angina), peripheral artery disease, subcortical vascular dementia, and intestinal ischemia (e.g., colon ischemia, acute mesenteric ischemia)
- Thrombosis and thromboembolism: acute coronary syndrome, stroke
- Renovascular hypertension
Traditional ASCVD risk factors 
Nonmodifiable risk factors
- Advancing age
- Male sex
- Race and ethnicity
- Modifiable risk factors
ASCVD risk-enhancing factors 
These parameters can be used to upwardly revise the risk assessment for patients with borderline or intermediate ASCVD risk. 
- Family history
- Patient history
- Diagnostic findings
ASCVD risk assessment is not recommended in individuals who are considered at high risk for ASCVD events, e.g., those with established ASCVD, familial hypercholesterolemia, and/or LDL cholesterol levels ≥ 190 mg/dL. 
General principles 
- For adults aged 20–75 years with unknown ASCVD risk : 
- Starting at age 20, reassess at least every 4–6 years.
- Reassess more frequently in adults aged 40–75 years, depending on the individual ASCVD risk. 
- Medical history, including smoking history
- Diabetes mellitus screening: Measure hemoglobin A1C.
Screening for hypertension
- Assess for ↑ systolic blood pressure.
- Ask about current antihypertensive treatment.
- Screening for lipid disorders: Assess for ↑ total cholesterol and ↓ HDL.
ASCVD risk calculation 
ASCVD risk calculators 
Pooled cohort equations (recommended) 
- Uses traditional ASCVD risk factors to estimate:
- Underestimates risk in individuals with: 
- May overestimate risk for individuals with the ability to access care and adhere to
- Other clinical calculators: Consider using for patients from the same populations used to validate the calculators. 
Risk calculators like the PCE should be used in patients at risk for ASCVD; they are not intended for patients with established ASCVD.
10-year ASCVD risk categories
- Low risk: < 5%
- Borderline risk: 5–7.4%
- Intermediate risk: 7.5–19.9%
- High risk: ≥ 20%
Additional evaluation 
- Review family and medical history for risk-enhancing factors, e.g., premature ASCVD in a first-degree relative.
- Obtain studies as indicated, e.g.:
- Advanced lipid testing: Increased levels are associated with a high lifetime risk of ASCVD.
- High-sensitivity CRP ≥ 2 mg/L: associated with inflammatory conditions
- Resting ankle-brachial index < 0.9: indicates reduced peripheral blood flow in lower extremities
Low-dose cardiac CT scan 
- Consider if there is remaining uncertainty about statin therapy after considering ASCVD risk-enhancing factors.
- Coronary artery calcium (CAC) score is calculated from the amount of calcification in the coronary arteries. 
Although ASCVD risk calculators are important tools for guiding primary prevention strategies in individuals with no history of ASCVD, results should always be considered in conjunction with other factors, e.g., ASCVD risk-enhancing factors, , and patient preferences.
General principles 
- Encourage all individuals to adhere to .
- Consider pharmacological prevention (e.g., statins and/or aspirin) based on estimated ASCVD risk.
- Utilize shared decision-making to tailor preventive therapies.
Manage modifiable risk factors for ASCVD, e.g.:
Lifestyle modifications for ASCVD prevention 
- Smoking cessation: Assess tobacco use at each encounter.
- Dietary modification with a heart-healthy diet, e.g.: 
- Physical activity: Provide .
- Sleep hygiene: Encourage 6–8 hours of sleep per night.
Pharmacological prevention 
Recommendations for preventive therapy vary.
|Indications for statins for primary ASCVD prevention|
|2019 American Heart association (AHA) guideline on primary prevention of cardiovascular disease ||2022 USPSTF recommendation on statin use for primary prevention of cardiovascular disease |
|Age 20–39 years|| |
|Age 40–75 years|| |
Preventive aspirin 
Consider only for patients with a low risk of bleeding, and use shared decision-making.
- The USPSTF recommends considering low-dose aspirin for adults aged 40–59 years with 10-year ASCVD risk > 10%. 
- According to the AHA, low-dose aspirin may be considered for certain adults aged 40–70 years with an increased ASCVD risk. 
Remember the ABCDS of ASCVD primary prevention: Aspirin (if there are indications), Blood pressure control, Cholesterol management, Diabetes management, Smoking cessation. 
General principles 
- Encourage .
- Assess risk for recurrent ASCVD events.
- Provide pharmacotherapy.
- Manage modifiable risk factors for ASCVD, e.g.:
Risk assessment for recurrent ASCVD events 
Patients with ASCVD are considered at very high risk of future ASCVD events in the following scenarios:
≥ 2 major ASCVD events, e.g.:
- 12 months in the past
1 major ASCVD event in combination with ≥ 2 high-risk conditions, e.g.:
- Age ≥ 65 years
- Current smoking
- LDL cholesterol ≥ 100 mg/dL on maximally tolerated statin therapy and ezetimibe
- History of coronary revascularization not associated with the major ASCVD event(s)
- Heterozygous familial hypercholesterolemia
- Comorbidities: e.g., diabetes mellitus, hypertension, , history of congestive heart failure
Lipid-lowering therapy for ASCVD
Statin therapy 
- is recommended in adults with established ASCVD.
- is a reasonable alternative for adults with ASCVD who:
Overview of statin intensity 
High-intensity statin therapy
|Moderate-intensity statin therapy|
|Low-intensity statin therapy|
Nonstatin lipid-lowering agents 
- Consider addition for patients with very high-risk ASCVD events with LDL cholesterol level ≥ 70 mg/dL despite maximally tolerated statin dose.
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